GPR40: Difference between revisions

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New page: <includeonly></includeonly>==Human GPR40 (hGPR40), also known as Free Fatty Acid Receptor 1 (FFAR1)== <StructureSection load='Sele4phu.pdb' size='400' side='right' caption='Human G-Protein...
 
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<includeonly></includeonly>==Human GPR40 (hGPR40), also known as Free Fatty Acid Receptor 1 (FFAR1)==
{{BAMBED
|DATE=June 14, 2016
|OLDID=2607462
|BAMBEDDOI=10.1002/bmb.21026
}}
 
==Human GPR40 (hGPR40), also known as Free Fatty Acid Receptor 1 (FFAR1)==
<StructureSection load='Sele4phu.pdb' size='400' side='right' caption='Human G-Protein Receptor 40 (hGPR40) visualized at 2.3 Å resolution by X-ray crystallography (PDB: [http://www.rcsb.org/pdb/explore/explore.do?structureId=4phu 4PHU]). The natural substrates of this protein are free fatty acids, giving rise to its secondary name, Free Fatty Acid Receptor 1 (FFAR1).' scene='72/727085/Hgpr40_begin/2'>   
<StructureSection load='Sele4phu.pdb' size='400' side='right' caption='Human G-Protein Receptor 40 (hGPR40) visualized at 2.3 Å resolution by X-ray crystallography (PDB: [http://www.rcsb.org/pdb/explore/explore.do?structureId=4phu 4PHU]). The natural substrates of this protein are free fatty acids, giving rise to its secondary name, Free Fatty Acid Receptor 1 (FFAR1).' scene='72/727085/Hgpr40_begin/2'>   


== Background ==
== Background ==
Human G-protein coupled receptor 40 (hGPR40), also known as free fatty acid 1 receptor (FFAR1), is a seven helical transmembrane domain receptor that recognizes long-chain free [https://en.wikipedia.org/wiki/Fatty_acid fatty acids] and induces insulin secretion.<ref name="Srivastava">PMID:25043059</ref> Some known fatty acid substrates of hGPR40 include [http://www.news-medical.net/health/What-is-Linoleic-Acid.aspx linoleic acid], [http://www.livestrong.com/article/438717-what-is-oleic-acid/ oleic acid], [http://www.hmdb.ca/metabolites/hmdb02925 eicosatrienoic acid], and [https://en.wikipedia.org/wiki/Palmitoleic_acid palmitoleic acid]<ref name="Morgan">PMID:19660440</ref>. hGPR40 is highly expressed in human pancreatic [https://en.wikipedia.org/wiki/Beta_cell β cells], brain, and endocrine cells of the [https://en.wikipedia.org/wiki/Gastrointestinal_tract gastrointestinal tract].<ref name = "RenXM">PMID:26974599</ref> hGPR40 is of particular interest because the triggering of insulin secrection is [https://en.wikipedia.org/wiki/Glucose glucose] dependent.This glucose-dependence for hGPR40 signaling makes it a target for the treatment of [https://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 type-2 diabetes] as agonists could increase glycemic control and lower the risk of hypoglycemia.<ref name="Srivastava"/> GPR40 is a member of a group of homologous [[GPCRs]] all located on chromosome 19q13.1 including GPCR41, 42, and 43.<ref name="Burant">PMID:23882043</ref>  
Human '''G-protein coupled receptor 40''' (hGPR40), also known as '''free fatty acid 1 receptor''' (FFAR1), is a seven helical transmembrane domain receptor that recognizes long-chain free [https://en.wikipedia.org/wiki/Fatty_acid fatty acids] and induces insulin secretion.<ref name="Srivastava">PMID:25043059</ref> Some known fatty acid substrates of hGPR40 include [http://www.news-medical.net/health/What-is-Linoleic-Acid.aspx linoleic acid], [http://www.livestrong.com/article/438717-what-is-oleic-acid/ oleic acid], [http://www.hmdb.ca/metabolites/hmdb02925 eicosatrienoic acid], and [https://en.wikipedia.org/wiki/Palmitoleic_acid palmitoleic acid]<ref name="Morgan">PMID:19660440</ref>. hGPR40 is highly expressed in human pancreatic [https://en.wikipedia.org/wiki/Beta_cell β cells], brain, and endocrine cells of the [https://en.wikipedia.org/wiki/Gastrointestinal_tract gastrointestinal tract].<ref name = "RenXM">PMID:26974599</ref> hGPR40 is of particular interest because the triggering of insulin secrection is [https://en.wikipedia.org/wiki/Glucose glucose] dependent.This glucose-dependence for hGPR40 signaling makes it a target for the treatment of [https://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 type-2 diabetes] as agonists could increase glycemic control and lower the risk of hypoglycemia.<ref name="Srivastava"/> GPR40 is a member of a group of homologous [[GPCRs]] all located on chromosome 19q13.1 including GPCR41, 42, and 43.<ref name="Burant">PMID:23882043</ref>  


== Function ==
== Function ==
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=== Other Potential Inhibitors ===
=== Other Potential Inhibitors ===
TAK-875 had the most promising outlooks of any current known agonists of hGPR40, but clinical trials were discontinued. Some other agonists tested in clinical trials include AMG-837 and AM-1638. When coadministered, AMG-837 and AM-1638 enhanced glucose tolerance, but they were found to be toxic in the human trials. Some other agonsits are currently being examined as well. One compound, LY 2881835 (Eli Lilly & Company, Indianapolis, IN), has undergone clinical trials, but the results are unknown. In addition to the above-mentioned compound, other orally bioavailable GPR40-specific agonists are currently in preclinical or clinical  development. As of 2015, TUG-770 and CNX-011-67 (Connexios Life Sciences, Karnataka, India) were in preclinical trials and JTT-851 (Japan Tobacco, Toyko, Japan), and P11187 (Piramal, Mumbai, India) were in clinical trails.<ref name="Mancini">PMID: 25604916</ref>  
TAK-875 had the most promising outlooks of any current known agonists of hGPR40, but clinical trials were discontinued. Some other agonists tested in clinical trials include AMG-837 and AM-1638. When coadministered, AMG-837 and AM-1638 enhanced glucose tolerance, but they were found to be toxic in the human trials. Some other agonsits are currently being examined as well. One compound, LY 2881835 (Eli Lilly & Company, Indianapolis, IN), has undergone clinical trials, but the results are unknown. In addition to the above-mentioned compound, other orally bioavailable GPR40-specific agonists are currently in preclinical or clinical  development. As of 2015, TUG-770 and CNX-011-67 (Connexios Life Sciences, Karnataka, India) were in preclinical trials and JTT-851 (Japan Tobacco, Toyko, Japan), and P11187 (Piramal, Mumbai, India) were in clinical trails.<ref name="Mancini">PMID: 25604916</ref>  
== 3D Structures of GPR40 ==
Updated on {{REVISIONDAY2}}-{{MONTHNAME|{{REVISIONMONTH}}}}-{{REVISIONYEAR}}
[[4phu]], [[5kw2]] – hGPR40/lysozyme + agonist – human <br />
[[5tzy]], [[5tzr]] – hGPR40/lysozyme (mutant) + partial agonist  <br />


== References ==
== References ==
<references/>
<references/>
 
[[Category:Topic Page]]
==Proteopedia Resources==
==Proteopedia Resources==
[http://proteopedia.org/wiki/index.php/Category:Gpr40 Category:GPR40]
[http://proteopedia.org/wiki/index.php/Category:Gpr40 Category:GPR40]
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[http://proteopedia.org/wiki/index.php/User:R._Jeremy_Johnson/CH462:Biochemistry_II_Butler_University Butler University Proteopedia Pages]
[http://proteopedia.org/wiki/index.php/User:R._Jeremy_Johnson/CH462:Biochemistry_II_Butler_University Butler University Proteopedia Pages]


See also:
*[[Receptor]]
*[[Transmembrane (cell surface) receptors]]
*[[G protein-coupled receptors]]
</StructureSection>
</StructureSection>
==Student Contributors==
==Student Contributors==
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Brittany Stankavich
Brittany Stankavich
[[Category:Featured in BAMBED]]
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